- Enhanced cytotoxicity of benzimidazole carbamate derivatives and solubilisation by encapsulation in cucurbit[n]uril
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The albendazole derivatives (2-methoxyethyl) 5-propylthio-1H-benzimidazole- 2-yl carbamate (MEABZ), N1-(2-methoxyethoxycarbonyl)-2-amino-5- propylthiobenzimidazole and N1-(2-methoxyethoxycarbonyl)-2-amino-6- propylthiobenzimidazole (MEABZ isomers A and B) and (2-hydroxyethyl) 5-propylthio-1H-benzimidazole-2-yl carbamate (HEABZ) have been synthesised. The cytotoxicity of these compounds was evaluated against a human colorectal cancer cell line (HT-29) and a human prostate cancer cell line (PC-3). The results demonstrate MEABZ, a new benzimidazole, is up to ten times more cytotoxic than the parent drug albendazole, whereas the MEABZ isomers A and B and HEABZ show no activity. A comparison of the cytotoxicity of these compounds, relative to ABZ, provides structure-activity data for this important class of anticancer agents. The aqueous solubilities of MEABZ encapsulated in Q[n] have been determined by 1H NMR spectroscopy. The aqueous solubility of MEABZ at a physiologically relevant pH increased by 1200-fold by encapsulation in Q[8], from 8 μM to 9.4 mM, while Q[6,7] encapsulation substantially increased the solubility to more than 2 mM. Encapsulation in Q[7] and Q[8] induced significant upfield shifts for the MEABZ propyl and benzimidazole resonances. The upfield shifts indicate that the propyl and benzimidazole protons are located within the Q[7] and Q[8] cavity upon encapsulation. By contrast, encapsulation in Q[6] induced large upfield shifts for the 1H resonances from the carbamate functional group, indicating that MEABZ associates with Q[6] at its portals, with only the carbamate group binding within the cavity. The Royal Society of Chemistry 2010.
- Zhao, Yunjie,Pourgholami, Mohammad H.,Morris, David L.,Collins, J. Grant,Day, Anthony I.
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Read Online
- CONJUGATES
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The present invention provides a conjugate of formula (I) and itsuse in methods of treatment, and also methods for delivering an active agent into a cell. The methods may be used to deliver an active agent into a nematode, flatworm, parasite or bacterium. The conjugate of formula (I) is: (formula (I)), wherein -D- is C1-4 alkylene or C2-4 alkenylene, preferably C2-4 alkenylene, where the alkylene or alkenylene is optionally substituted with alkyl or halo; A- is an active agent for delivery; and -RA, -RB, -RT1, -RT2, -R1, -R2, -R3, -X- and -L- are as defined herein.
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Page/Page column 84-85
(2020/07/14)
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- Synthesis, characterization and antiparasitic activity of organometallic derivatives of the anthelmintic drug albendazole
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Helminthiases, a group of neglected tropical diseases, affect more than one billion people mainly in tropical and subtropical regions. Moreover, major intestinal protozoa have a significant impact on global public health. Albendazole (ABZ) is a broad-spectrum anthelmintic recommended by the World Health Organisation (WHO). However, drug resistance is emerging due to its widespread use. In order to tackle this problem, taking into account the spectacular results obtained with ferroquine, an organometallic derivatization of the antimalarial drug chloroquine, we have prepared, in this study, a series of new ferrocenyl and ruthenocenyl derivatives of the organic drug ABZ and assessed their activity against different helminths and protozoans, namely Trichuris muris, Heligmosomoides polygygrus, Schistosoma mansoni, Giardia lamblia, Haemonchus contortus and Toxoplasma gondii. The ferrocene-containing ABZ analogue 2d exhibited over 70% activity against T. muris adults in vitro at 200 μM and no toxicity to mammalian cells (IC50 >100 μM). H. polygyrus adults were not affected by any of the derivatives tested. Against T. gondii, the ferrocene-containing ABZ analogues 1a and 2d showed better in vitro activity than ABZ and low toxicity to the host cells. The activity of the analogous ruthenocenyl compound 2b against S. mansoni and T. gondii in vitro might be attributed to its toxicity towards the host cells rather than a specific antiparasitic activity. These results demonstrate that the derivatives show a species specific in vitro activity and the choice of the organometallic moieties attached to the organic drug is playing a very important role. Two of our organometallic compounds, namely 1b and 2d, were tested in T. muris infected mice. At a 400 mg kg-1 dose, the compounds showed moderate worm burden reductions but low worm expulsion rates. Overall, this work, which is one of the first studies reporting the potential of organometallic compounds on a very broad range of parasitic helminths and protozoan, is a clear confirmation of the potential of organometallic complexes against parasites of medical and veterinary importance.
- Anghel, Nicoleta,Blacque, Olivier,Bouchene, Rafika,Cariou, Kevin,Gasser, Gilles,Gasser, Robin B.,H?berli, Cécile,Hemphill, Andrew,Karges, Johannes,Keiser, Jennifer,Keller, Sarah,Lin, Yan,Müller, Joachim,Manoury, Eric,Ong, Yih Ching,Taki, Aya C.
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p. 6616 - 6626
(2020/06/08)
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- Albendazole hapten and preparation method and application thereof
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The invention relates to the field of hapten preparation, in particular to albendazole hapten and a preparation method and application thereof. The albendazole hapten has a structure shown by a formula I, and is prepared by taking albendazole and hydrochloric acid as raw materials through reaction in a preparation process. The hapten and carrier protein are coupled to prepare albendazole holoantigen, and an albendazole antibody can be further prepared. The albendazole hapten provided by the invention contains an amino terminal, can be coupled with a carrier without changing the structure, is easier to expose a specific binding site after being connected with the carrier protein, and has higher sensitivity; the synthesis method of the albendazole hapten is simple, and the yield and the purity are high; and the prepared albendazole antibody has broad-spectrum recognition performance and high sensitivity, and has good application prospect in albendazole related residue detection.
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Paragraph 0043; 0044-0052
(2019/06/30)
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- Biology-oriented drug synthesis (BIODS), structural characterization and bioactivities of novel albendazole derivatives
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Background: Albendazole is a drug, belongs to the family of benzimidazole, and used as an anthelmintic agent in both human and veterinary medicine. It is marketed as Albenza which is used for the treatment of a variety of parasitic worm infestations such
- Khan, Momin,Khan, Shahid,Salar, Uzma,Khan, Khalid Mohammed,Rehman, Gauhar,Gul, Naeem,Khan, Iltaf
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p. 1329 - 1338
(2019/11/22)
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- Diethylenetriamine-Mediated Direct Cleavage of Unactivated Carbamates and Ureas
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Diethylenetriamine is effective for the direct cleavage of unactivated carbamates and ureas without additional reagents and catalysts. Various carbamates and ureas were cleaved to afford products in good yield, and the reactions were not affected by air or moisture. Unique chemoselective cleavage of carbamate and urea in the presence of amides was also achieved.
- Noshita, Megumi,Shimizu, Yuhei,Morimoto, Hiroyuki,Ohshima, Takashi
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supporting information
p. 6062 - 6065
(2016/12/09)
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